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Why a DNA with a high GC content more stable than one with a less GC content? Is it because of the three hydrogen bonds in GC base pair which is one more than a AT base pair or is it because of the more stable base stacking of GC base pairs? In my book it is given that it is due to the hydrogen bonds but in a research article I found it is saying that base stacking solely determines thermal stability. enter link description here

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Although taken in isolation GC bonds should be more stable than AT bonds, due to their higher binding energy (three hydrogen bodns versus two), it is the stacking energy that is considered the stabilizing factor of the DNA:

We find that temperature and salt dependences of the stacking term fully determine the temperature and the salt dependence of DNA stability parameters. For all temperatures and salt concentrations employed in present study, base-stacking is the main stabilizing factor in the DNA double helix. A•T pairing is always destabilizing and G•C pairing contributes almost no stabilization. Base-stacking interaction dominates not only in the duplex overall stability but also significantly contributes into the dependence of the duplex stability on its sequence.

The reason for that is that one can have the same number of pairs under many different configurations of strands, which means high entropy and instability, unless there are stacking interactions. This is why most models of DNA and RNA helices are based on adding the stacking energies, although there are some additional contributions, particularly in the case of RNA - initiation energy, energies associated to the inner loops, etc.

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